Have No Fear, Mice Are Here

This nice report from PBS Chicago describes how researchers at Northwestern University are using mice to study post-traumatic stress disorder, and get at the basic mechanisms of fear. They already have positive results with experimental drugs that could eventually be used to treat people and prevent traumatic memories from taking over their lives — whether they are soldiers in combat or civilians caught up in a natural disaster.

Jelena Radulovic and colleagues at Northwestern’s ‘fear lab’ stress mice by first immobilizing them for an hour, then giving them a mild electrical shock. They can see changes in their behavior — fearful mice ‘freeze’ and don’t explore their surroundings.

They can look at chemical changes in the brains of these mice to see what happens as these stressful memories are made.

And now they have been able to test two new anti-anxiety drugs, finding that they can prevent this “mouse PTSD.” Because these drugs are related to one already approved for human use, human clinical trials could come relatively soon, according to the report.

Is it ethical to upset mice with the aim of producing drugs that could bring such benefits? Radulovic certainly thinks so, and I would agree. She says: “We are considering ethical problems all the time in the lab, and we are designing the experiments so that there is a minimal possible distress incurred to the animals in order to model human disorder.”

I’d add that her study would have had to clear Northwestern’s Institutional Animal Care and Use Committee, and assuming it was funded by the National Institutes of Health would also have had to pass ethics review there.

In addition to psychological trauma, there are also many cases where people lose a limb to disease or physical trauma. Research such as that described at the following link helps to discover and develop innovative medical prostheses:

The integration of sensors that can transmit sensory information to implants in the brain is the next major hurdle to overcome, though the work of Bensmaia and Hatsopoulos, and others such as Miguel Nicolelis at Duke University, is progressing rapidly towards methods to overcome these difficulties.

Post traumatic stress disorder is an increasingly common, serious mental disorder that affects soldiers returning from war, victims of domestic violence and rape and children who are subject to abuse. PTSD involves dysregulation of the circuits in the brain that coordinate normal fear reactions, leading to the characteristic signs of the illness – which include mentally and emotionally re-experiencing the trauma (flashbacks), abnormal avoidance behavior and hypervigilance. Other complications include emotional numbing, sleep disorders and dramatically increased risk for alcoholism and drug abuse.

The fear circuitry of the brain is remarkably conserved across mammals. When a mouse freezes in reaction to seeing a predatory cat, or when a human freezes when a gun is pulled on them, their respective brains are processing the threat and engaging a behavioral response via almost identical mechanisms. Thanks to Kluver and Bucy and their studies of monkeys in the mid-20th century, we now know that this circuit includes portions of the temporal lobe – most notably the amygdala.

Today, researchers are able to use mice in their studies that are aimed at PREVENTING PTSD. Once this condition has developed, it is very refractory to treatments, but new data from animal models suggests that it is possible to prevent it by pharmacological interventions given soon in time after the trauma. Treatments discovered in animals are today being evaluated in ERs. This is yet another example of where basic science studies in animals are leading the way to novel treatments that couldn’t have been anticipated or discovered solely by studying human patients.